The specific problems produced differ according to the particular abnormal synthesis involved. Common manifestations include ataxia; seizures; retinopathy; liver fibrosis; coagulopathies; failure to thrive; dysmorphic features ("e.g.," inverted nipples and subcutaneous fat pads; and strabismus. If an MRI is obtained, cerebellar atrophy and hypoplasia is a common finding.

Ocular abnormalities of CDG-Ia include: myopia, infantile esotropia, delayed visual maturation, low vision, optic disc pallor, and reduced rod function on electroretinography.

Three subtypes of CDG I (a,b,d) can cause congenital hyperinsulinism with hyperinsulinemic hypoglycemia in infancy.

Mutations in several genes have been associated with the traditional clinical syndromes, termed muscular dystrophy-dystroglycanopathies (MDDG). A new nomenclature based on clinical severity and genetic cause was recently proposed by OMIM. The severity classifications are A (severe), B (intermediate), and C (mild). The subtypes are numbered one to six according to the genetic cause, in the following order: (1) POMT1, (2) POMT2, (3) POMGNT1, (4) FKTN, (5) FKRP, and (6) LARGE.

Most common severe types include:

The following are symptoms characteristic with individuals having the disorder. Individuals may display some, most, or all of these symptoms throughout the course of their life, though symptoms may vary with each patient.

- Abnormal hair (coarse, thick, brittle)

- Calvarial hypomineralization (soft skull)

- Y-shaped cataracts by 1–2 years of age

- Skeletal defects

- Hypertelorism (wide-set eyes)

- Facial dysmorphisms

- Late-closing fontanels

- Abnormal accumulation of proteins in the endoplasmic reticulum

- Scoliosis

- Broad forehead, nose

- Missing, small teeth or abnormal teeth positioning

- Poor skull calcification

- Flat foot

- Motor delay

- Abnormal vertebrae

- Prominent forehead and brow

- High nose bridge

- Capillary hemangioma

- Delayed tooth eruption

- Long upper lip groove

- Large mouth

- High arched palate

- Narrow hips and rib cage

- Thin lips

- Narrow and sloping shoulders

- Hyperpigmentation

- Hyperextensible joints

Onset of the disease is in neonatal development and infancy, and symptoms tend to become evident soon after birth.

These are pleomorphic and include

- dolichocephaly (with or without sagittal suture synostosis)

- microcephaly

- pre- and postnatal growth retardation

- brachydactyly

- narrow thorax

- rhizomelic dwarfism

- epicanthal folds

- hypodontia and/or microdontia

- sparse, slow-growing, hyperpigmented, fine hair

- nail dysplasia

- hypohydrosis

- chronic renal failure

- heart defects

- liver fibrosis

- visual deficits

- photophobia

- hypoplasia of the posterior corpus callosum

- aberrant calcium homeostasis

Electroretinography shows gross abnormalities.

Two fetuses of 19 and 23 weeks gestation have also been reported. They showed acromesomelic shortening, craniofacial characteristics with absence of craniosynostosis, small kidneys with tubular and glomerular microscopic cysts, persistent ductal plate with portal fibrosis in the liver, small adrenals, an enlarged cisterna magna and a posterior fossa cyst.

The presentation of this condition includes a characteristic facies. The cardiac manifestations include patent ductus arteriosus, congenital hypertrophy of the left ventricle, and pericardial effusions.

Neurodevelopmental outcome appears normal, but obsessive traits and anxiety have been reported. It may also be associated with recurrent infections with low immunoglobulin levels and gastric bleeding, and additional possible associations include lymphoedema and heterochromia iridis.

Sensenbrenner syndrome (OMIM #218330) is a rare (less than 20 cases reported by 2010) multisystem disease first described in 1975. It is inherited in an autosomal recessive fashion, and a number of genes appear to be responsible. Three genes responsible have been identified: intraflagellar transport (IFT)122 (WDR10), IFT43 — a subunit of the IFT complex A machinery of primary cilia, and WDR35 (IFT121: TULP4)

It is also known as Sensenbrenner–Dorst–Owens syndrome, Levin Syndrome I and cranioectodermal dysplasia (CED)

D-Bifunctional protein deficiency (officially called 17β-hydroxysteroid dehydrogenase IV deficiency) is an autosomal recessive peroxisomal fatty acid oxidation disorder. Peroxisomal disorders are usually caused by a combination of peroxisomal assembly defects or by deficiencies of specific peroxisomal enzymes. The peroxisome is an organelle in the cell similar to the lysosome that functions to detoxify the cell. Peroxisomes contain many different enzymes, such as catalase, and their main function is to neutralize free radicals and detoxify drugs, such as alcohol. For this reason peroxisomes are ubiquitous in the liver and kidney. D-BP deficiency is the most severe peroxisomal disorder, often resembling Zellweger syndrome.

Characteristics of the disorder include neonatal hypotonia and seizures, occurring mostly within the first month of life, as well as visual and hearing impairment. Other symptoms include severe craniofacial disfiguration, psychomotor delay, and neuronal migration defects. Most onsets of the disorder begin in the gestational weeks of development and most affected individuals die within the first two years of life.

Cranio–lenticulo–sutural dysplasia (CLSD, or Boyadjiev-Jabs syndrome) is a neonatal/infancy disease caused by a disorder in the 14th chromosome. It is an autosomal recessive disorder, meaning that both recessive genes must be inherited from each parent in order for the disease to manifest itself. The disease causes a significant dilation of the endoplasmic reticulum in fibroblasts of the host with CLSD. Due to the distension of the endoplasmic reticulum, export of proteins (such as collagen) from the cell is disrupted.

The production of SEC23A protein is involved in the pathway of exporting collagen (the COPII pathway), but a missense mutation causes and underproduction of SEC23A which inhibits the pathway, affecting collagen secretion. This decrease in collagen secretion can lead to the bone defects that are also characteristic of the disease, such as skeletal dysplasia and under-ossification. Decreased collagen in CLSD-affected individuals contributes to improper bone formation, because collagen is a major protein in the extracellular matrix and contributes to its proper mineralization in bones. It has also been hypothesized that there are other defects in the genetic code besides SEC23A that contribute to the disorder.

The clinical manifestations present at birth are generalized hypotonia, muscle weakness, developmental delay with mental retardation and occasional seizures. The congenital muscular dystrophy is characterized by hypoglycosylation of α-dystroglycan.

Those born with the disease also experience severe ocular and brain defects. Half of all children with WWS are born with encephalocele, which is a gap in the skull that will not seal. The meninges of the brain protrude through this gap due to the neural tube failing to close during development. A malformation of the a baby's cerebellum is often a sign of this disease.Common ocular issues associated with WWS are abnormally small eyes and retinal abnormalities cause by an underdeveloped light-sensitive area in the back of the eye.

Congenital generalized lipodystrophy (CGL) is a rare autosomal recessive disorder which manifests with insulin resistance, absence of subcutaneous fat and muscular hypertrophy. Homozygous or compound heterozygous mutations in four genes are associated with the four subtypes of CGL. The condition appears in early childhood with accelerated linear growth, quick aging of bones, and a large appetite. As the child grows up, acanthosis nigricans (hyperpigmentation and thickening of skin) will begin to present itself throughout the body – mainly in the neck, trunk, and groin. The disorder also has characteristic features like hepatomegaly or an enlarged liver which arises from fatty liver and may lead to cirrhosis, muscle hypertrophy, lack of adipose tissue, splenomegaly, hirsutism (excessive hairiness) and hypertriglyceridemia. Fatty liver and muscle hypertrophy arise from the fact that lipids are instead stored in these areas; whereas in a healthy individual, lipids are distributed more uniformly throughout the body subcutaneously. The absence of adipose tissue where they normally occur causes the body to store fat in the remaining areas. Common cardiovascular problems related to this syndrome are cardiac hypertrophy and arterial hypertension (high blood pressure). This disorder can also cause metabolic syndrome. Most with the disorder also have a prominent umbilicus or umbilical hernia. Commonly, patients will also have acromegaly with enlargement of the hands, feet, and jaw. After puberty, additional symptoms can develop. In women, clitoromegaly and polycystic ovary syndrome can develop. This impairs fertility for women, and only a few documented cases of successful pregnancies in women with CGL exist. However, the fertility of men with the disorder is unaffected.

Cantú syndrome (hypertrychotic osteochondrodysplasia) is a rare condition characterized by hypertrichosis, osteochondrodysplasia, and cardiomegaly. Less than 50 cases have been described in the literature; they are associated with a mutation in the "ABCC9"-gene that codes for the ABCC9-protein.

Congenital generalized lipodystrophy (also known as Berardinelli–Seip syndrome) is an extremely rare autosomal recessive skin condition, characterized by an extreme scarcity of fat in the subcutaneous tissues. It is a type of lipodystophy disorder where the magnitude of fat loss determines the severity of metabolic complications. Only 250 cases of the condition have been reported, and it is estimated that it occurs in 1 in 10 million people worldwide.

Nijmegen breakage syndrome (NBS), also known as Berlin breakage syndrome, ataxia telangiectasia variant 1 (AT-V1) and Seemanova syndrome, is a rare autosomal recessive congenital disorder causing chromosomal instability, probably as a result of a defect in the double Holliday junction DNA repair mechanism and/or the synthesis dependent strand annealing mechanism for repairing double strand breaks in DNA (see Homologous recombination).

NBS1 codes for a protein (nibrin) that has two major functions: (1) to stop the cell cycle in the S phase, when there are errors in the cell DNA (2) to interact with FANCD2 that can activate the BRCA1/BRCA2 pathway of DNA repair. This explains why mutations in the NBS1 gene lead to higher levels of cancer (see Fanconi anemia, Cockayne syndrome.)

The name derives from the Dutch city Nijmegen where the condition was first described.

Most people with NBS have West Slavic origins. The largest number of them live in Poland.

Walker–Warburg syndrome (WWS), also called Warburg syndrome, Chemke syndrome, HARD syndrome (Hydrocephalus, Agyria and Retinal Dysplasia), Pagon syndrome, cerebroocular dysgenesis (COD) or cerebroocular dysplasia-muscular dystrophy syndrome (COD-MD), is a rare form of autosomal recessive congenital muscular dystrophy. It is associated with brain (lissencephaly, hydrocephalus, cerebellar malformations) and eye abnormalities. This condition has a worldwide distribution. The overall incidence is unknown but a survey in North-eastern Italy has reported an incidence rate of 1.2 per 100,000 live births. It is the most severe form of congenital muscular dystrophy with most children dying before the age of three years.

This defect leads to a multi-systemic disorder of the connective tissue, muscles, central nervous system (CNS), and cardiovascular system. Homocystinuria represents a group of hereditary metabolic disorders characterized by an accumulation of the amino acid homocysteine in the serum and an increased excretion of homocysteine in the urine. Infants appear to be normal and early symptoms, if any are present, are vague.

Signs and symptoms of homocystinuria that may be seen include the following:

Affected individuals present with a broad array of medical and behavioral manifestations (tables 1 and 2). Patients are consistently characterized by global developmental delay, intellectual disability, speech abnormalities, ASD-like behaviors, hypotonia and mild dysmorphic features. Table 1 summarizes the dysmorphic and medical conditions that have been reported in individuals with PMS. Table 2 summarize the psychiatric and neurological associated with PMS. Most of the studies include small samples or relied on parental report or medical record review to collect information, which can account in part for the variability in the presentation of some of the presenting features. Larger prospective studies are needed to further characterize the phenotype.

Table 1: Dysmorphic features and medical comorbid conditions that have been reported in individuals with Phelan McDermid Syndrome.

Table 2: Psychiatric and Neurologic Manifestations associated with Phelan McDermid Syndrome

Because of the enormous number of these diseases and wide range of systems affected, nearly every "presenting complaint" to a doctor may have a congenital metabolic disease as a possible cause, especially in childhood. The following are examples of potential manifestations affecting each of the major organ systems.

It is characterized by developmental defects including cryptophthalmos (where the eyelids fail to separate in each eye), and malformations in the genitals (such as micropenis, cryptorchidism or clitoromegaly). Congenital malformations of the nose, ears, larynx and renal system, as well as mental retardation, manifest occasionally. Syndactyly (fused fingers or toes) has also been noted.

Acrocallosal syndrome (also known as ACLS) is a rare autosomal recessive syndrome characterized by corpus callosum agenesis, polydactyly, multiple dysmorphic features, motor and mental retardation, and other symptoms. The syndrome was first described by Albert Schinzel in 1979.

It is associated with "GLI3".

Inborn errors of metabolism form a large class of genetic diseases involving congenital disorders of metabolism. The majority are due to defects of single genes that code for enzymes that facilitate conversion of various substances (substrates) into others (products). In most of the disorders, problems arise due to accumulation of substances which are toxic or interfere with normal function, or to the effects of reduced ability to synthesize essential compounds. Inborn errors of metabolism are now often referred to as congenital metabolic diseases or inherited metabolic diseases.

The term "inborn error of metabolism" was coined by a British physician, Archibald Garrod (1857–1936), in 1908. He is known for work that prefigured the "one gene-one enzyme" hypothesis, based on his studies on the nature and inheritance of alkaptonuria. His seminal text, "Inborn Errors of Metabolism" was published in 1923.

OA1 is recognized by many different symptoms. Reduced visual acuity is accompanied by involuntary movements of the eye termed as nystagmus. Astigmatism is a condition wherein there occurs significant refractive error. Moreover, ocular albino eyes become crossed, a condition called as ‘lazy eyes’ or strabismus. Since very little pigment is present the iris becomes translucent and reflects light back. It appears green to blueish red. However, the most important part of the eye, the fovea which is responsible for acute vision, does not develop properly, probably indicating the role of melanin in the development stages of the eye. Some affected individuals may also develop photophobia/photodysphoria. All these symptoms are due to lack of pigmentation of the retina. Moreover, in an ocular albino eye, nerves from back of the eye to the brain may not follow the usual pattern of routing. In an ocular albino eye, more nerves cross from back of the eye to the opposite side of the brain instead of going to the both sides of the brain as in a normal eye. An ocular albino eye appears blueish pink in color with no pigmentation at all unlike a normal eye. Carrier women have regions of hypo- and hyper-pigmentation due to X-inactivation and partial iris transillumination and do not show any other symptoms exhibited by those affected by OA1.

Ocular albinism type 1 (OA1), also called Nettleship–Falls syndrome, is the most common type of ocular albinism, with a prevalence rate of 1:50,000. It is an inheritable classical Mendelian type X-linked recessive disorder wherein the retinal pigment epithelium lacks pigment while hair and skin appear normal. Since it is usually an X-linked disorder, it occurs mostly in males, while females are carriers unless they are homozygous. About 60 missense and nonsense mutations, insertions, and deletions have been identified in "Oa1". Mutations in OA1 have been linked to defective glycosylation and thus improper intracellular transportation.

The eponyms of the name "Nettleship–Falls syndrome" are the ophthalmologists Edward Nettleship and Harold Francis Falls.

22q13 deletion syndrome (spoken as "twenty-two q one three", see Locus (genetics)) is a genetic disorder caused by deletions or rearrangements on the q terminal end (long arm) of chromosome 22. Any abnormal genetic variation in the q13 region that presents with significant manifestations (phenotype) typical of a terminal deletion may be diagnosed as 22q13 deletion syndrome. 22q13 deletion syndrome is often called Phelan-McDermid syndrome (abbreviated PMS). There is disagreement among researchers as to the exact definition of 22q13 deletion syndrome. The Developmental Synaptopathies Consortium defines PMS as being caused by "SHANK3" mutations, a definition that appears to exclude terminal deletions. The requirement to include "SHANK3" in the definition is supported by many, but not by those who first described 22q13 deletion syndrome.

A prototypical terminal deletion of 22q13 can be uncovered by karyotype analysis, but many terminal and interstitial deletions are too small. The availability of DNA microarray technology for revealing multiple genetic problems simultaneously has been the diagnostic tool of choice. The falling cost for whole exome sequencing and, eventually, whole genome sequencing, may replace DNA microarray technology for candidate evaluation. However, fluorescence in situ hybridization (FISH) tests remain valuable for diagnosing cases of mosaicism (mosaic genetics) and chromosomal rearrangements (e.g., ring chromosome, unbalanced chromosomal translocation). Although early researchers sought a monogenic (single gene genetic disorder) explanation, recent studies have not supported that hypothesis (see Etiology, below).

The various types of vWD present with varying degrees of bleeding tendency, usually in the form of easy bruising, nosebleeds, and bleeding gums. Women may experience heavy menstrual periods and blood loss during childbirth.

Severe internal bleeding and bleeding into joints are uncommon in all but the most severe type, vWD type 3.

Type 1 vWD (60-80% of all vWD cases) is a quantitative defect which is heterozygous for the defective gene. It can arise from failure to secrete vWF into the circulation or from vWF being cleared more quickly than normal. Decreased levels of vWF are detected at 20-50% of normal, i.e. 20-50 IU.

Many patients are asymptomatic or may have mild symptoms and not have clearly impaired clotting, which might suggest a bleeding disorder. Often, the discovery of vWD occurs incidentally to other medical procedures requiring a blood work-up. Most cases of type 1 vWD are never diagnosed due to the asymptomatic or mild presentation of type I and most people usually end up leading a normal life free of complications, with many being unaware that they have the disorder.

Trouble may, however, arise in some patients in the form of bleeding following surgery (including dental procedures), noticeable easy bruising, or menorrhagia (heavy menstrual periods). The minority of cases of type 1 may present with severe hemorrhagic symptoms.