Type 1 usually begins somewhere in the first three to 18 months of age and in considered the most severe of the three types. Symptoms include:

- Coarse facial features

- Enlarged liver, spleen, and/or heart

- Intellectual disability

- Seizures

- Abnormal bone formation of many bones

- Progressive deterioration of brain and spinal cord

- Increased or decreased perspiration

Patients have no vascular lesions, but have rapid psychomotor regression, severe and rapidly progressing neurologic signs, elevated sodium and chloride excretion in the sweat, and fatal outcome before the sixth year.

Type 2 appears when a child is around 18 months of age and in considered milder than Type 1 but still severe. Symptoms include:

- Symptoms similar to Type 1 but milder and progress more slowly.

Genetic changes are related to the following types of collagenopathy, types II and XI.

The system for classifying collagenopathies is changing as researchers learn more about the genetic causes of these disorders.The clinical features of the type II and XI collagenopathies vary among the disorders, but there is considerable overlap. Common signs and symptoms include problems with bone development that can result in short stature, enlarged joints, spinal curvature, and arthritis at a young age. For some people, bone changes can be seen only on X-ray images. Problems with vision and hearing, as well as a cleft palate with a small lower jaw, are common. Some individuals with these disorders have distinctive facial features such as protruding eyes and a flat nasal bridge.

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.

The type II and XI collagenopathies are a group of disorders that affect connective tissue, the tissue that supports the body's joints and organs. These disorders are caused by defects in type II or type XI collagen. Collagens are complex molecules that provide structure, strength, and elasticity to connective tissue. Type II and type XI collagen disorders are grouped together because both types of collagen are components of the cartilage found in joints and the spinal column, the inner ear, and the jelly-like substance that fills the eyeball (the vitreous). The type II and XI collagenopathies result in similar clinical features.

MPS III is characterized by severe deterioration of the central nervous system, resulting in a variety of symptoms. Individuals with Sanfilippo syndrome usually start to show the symptoms between the age of 2 to 6. Speech problems, hyperactivity, aggressive behavior, developmental delays, hirsutism, sleep disturbances, seizures are the common manifestation of the syndrome at the initial stage. After the age of 10, patients start to experience increasingly severe symptoms including loss of motor and cognitive skills and somatic diseases. Patients later enter vegetative state, eventually leading to death in their 30s.

Individuals with MPS III tend to have mild skeletal abnormalities; osteonecrosis of the femoral head may be present in patients with the severe form. Optical nerve atrophy, deafness, otitis can be seen in moderate to severe individuals. Other characteristics include coarse facial features, thick lips, synophrys, and stiff joints. Chronic diarrhea, enlarged liver and spleen are also common.

It is difficult to clinically distinguish differences among the four types of Sanflippo syndrome. However, MPS IIIA is usually the most severe subtype, characterized by earliest onset, rapid clinical progression with severe symptoms, and short survival.

The mucopolysaccharidoses share many clinical features but have varying degrees of severity. These features may not be apparent at birth but progress as storage of glycosaminoglycans affects bone, skeletal structure, connective tissues, and organs. Neurological complications may include damage to neurons (which send and receive signals throughout the body) as well as pain and impaired motor function. This results from compression of nerves or nerve roots in the spinal cord or in the peripheral nervous system, the part of the nervous system that connects the brain and spinal cord to sensory organs such as the eyes and to other organs, muscles, and tissues throughout the body.

Depending on the mucopolysaccharidosis subtype, affected individuals may have normal intellect or have cognitive impairments, may experience developmental delay, or may have severe behavioral problems. Many individuals have hearing loss, either conductive (in which pressure behind the eardrum causes fluid from the lining of the middle ear to build up and eventually congeal), neurosensory (in which tiny hair cells in the inner ear are damaged), or both. Communicating hydrocephalus—in which the normal reabsorption of cerebrospinal fluid is blocked and causes increased pressure inside the head—is common in some of the mucopolysaccharidoses. Surgically inserting a shunt into the brain can drain fluid. The eye's cornea often becomes cloudy from intracellular storage, and glaucoma and degeneration of the retina also may affect the patient's vision.

Physical symptoms generally include coarse or rough facial features (including a flat nasal bridge, thick lips, and enlarged mouth and tongue), short stature with disproportionately short trunk (dwarfism), dysplasia (abnormal bone size and/or shape) and other skeletal irregularities, thickened skin, enlarged organs such as liver (hepatomegaly) or spleen (splenomegaly), hernias, and excessive body hair growth. Short and often claw-like hands, progressive joint stiffness, and carpal tunnel syndrome can restrict hand mobility and function. Recurring respiratory infections are common, as are obstructive airway disease and obstructive sleep apnea. Many affected individuals also have heart disease, often involving enlarged or diseased heart valves.

Another lysosomal storage disease often confused with the mucopolysaccharidoses is mucolipidosis. In this disorder, excessive amounts of fatty materials known as lipids (another principal component of living cells) are stored, in addition to sugars. Persons with mucolipidosis may share some of the clinical features associated with the mucopolysaccharidoses (certain facial features, bony structure abnormalities, and damage to the brain), and increased amounts of the enzymes needed to break down the lipids are found in the blood.

MPS VII, Sly syndrome, one of the least common forms of the mucopolysaccharidoses, is estimated to occur in fewer than one in 250,000 births. The disorder is caused by deficiency of the enzyme beta-glucuronidase. In its rarest form, Sly syndrome causes children to be born with hydrops fetalis, in which extreme amounts of fluid are retained in the body. Survival is usually a few months or less. Most children with Sly syndrome are less severely affected. Neurological symptoms may include mild to moderate intellectual disability by age 3, communicating hydrocephalus, nerve entrapment, corneal clouding, and some loss of peripheral and night vision. Other symptoms include short stature, some skeletal irregularities, joint stiffness and restricted movement, and umbilical and/or inguinal hernias. Some patients may have repeated bouts of pneumonia during their first years of life. Most children with Sly syndrome live into the teenage or young adult years.

Symptoms range widely in their onset and severity. The onset of the most severe form, type III, begins within the first months of life and includes a quick progression of intellectual disability, liver and spleen enlargement (splenomegaly), hearing loss, respiratory infections and skeletal abnormalities. Often the appearance of an affected individual includes the following facial features: protruding forehead, leveled nasal bridge, small nose and wide mouth. Muscular weakness or spinal abnormalities can occur due to the buildup of storage materials in the muscle. A milder form of alpha-mannosidosis involves mild to moderate intellectual disability which develops during childhood or adolescence.

Symptoms of ML I are either present at birth or develop within the first year of life. In many infants with ML I, excessive swelling throughout the body is noted at birth. These infants are often born with coarse facial features, such as a flat nasal bridge, puffy eyelids, enlargement of the gums, and excessive tongue size (macroglossia). Many infants with ML I are also born with skeletal malformations such as hip dislocation. Infants often develop sudden involuntary muscle contractions (called myoclonus) and have red spots in their eyes (cherry red spots). They are often unable to coordinate voluntary movement (called ataxia). Tremors, impaired vision, and seizures also occur in children with ML I. Tests reveal abnormal enlargement of the liver (hepatomegaly) and spleen (splenomegaly) and extreme abdominal swelling. Infants with ML I generally lack muscle tone (hypotonia) and have mental retardation that is either initially or progressively severe. Many patients suffer from failure to thrive and from recurrent respiratory infections. Most infants with ML I die before the age of 1 year.

Collagen, type II, alpha 1 (primary osteoarthritis, spondyloepiphyseal dysplasia, congenital), also known as COL2A1, is a human gene that provides instructions for the production of the pro-alpha1(II) chain of type II collagen.

Patients with Sack–Barabas syndrome have thin, fragile skin, especially in the chest and abdomen, that bruises easily; hands and feet may have an aged appearance. Skin is soft but not overly stretchy.

Facial features are often distinctive, including protruding eyes, a thin nose and lips, sunken cheeks, and a small chin.

Other signs of the disorder include hypermobility of joints, tearing of tendons and muscles, painfully swollen veins in the legs, lung collapse, and slow wound healing following injury or surgery.

Infants with the condition may be born with hip dislocations and clubfeet.

Unpredictable ruptures of arteries and organs are serious complications of SBS. Ruptured arteries can cause internal bleeding, stroke, or shock, the most common cause of death in patients with this disorder.

Rupture of the intestine is seen in 25 to 30 percent of affected individuals and tearing of the uterus during pregnancy affects 2 to 3 percent of women. Although these symptoms are rare in childhood, more than 80 percent of patients experience severe complications by the age of 40. Teenage boys are at high risk for arterial rupture, often being fatal.

The symptoms of LSD vary, depending on the particular disorder and other variables such as the age of onset, and can be mild to severe. They can include developmental delay, movement disorders, seizures, dementia, deafness, and/or blindness. Some people with LSDhave enlarged livers (hepatomegaly) and enlarged spleens (splenomegaly), pulmonary and cardiac problems, and bones that grow abnormally.

It is characterized by a deficiency in biliary copper excretion that causes deformations in the skeleton. These include projections on the back of the skull (parasagittal bone exostoses arising from the occipital bone—the so-called "occipital horns") as well as deformities of the elbow, radial head dislocation, hammer-shaped lateral ends of the clavicles, and abnormalities of the hips and pelvis.

OHS presents in early to middle childhood. Children may present with features such as:

Sanfilippo syndrome, or mucopolysaccharidosis III (MPS-III) is a rare autosomal recessive lysosomal storage disease. It is caused by a deficiency in one of the enzymes needed to break down the glycosaminoglycan heparan sulfate (which is found in the extra-cellular matrix and on cell surface glycoproteins).

Although undegraded heparan sulfate is the primary stored substrate, glycolipids such as gangliosides are also stored despite no genetic defect in the enzymes associated with their breakdown.

The condition is named for Sylvester Sanfilippo, the pediatrician who first described the disease.

A defective alpha-mannosidase enzyme, which normally helps to break down complex sugars derived from glycoproteins in the lysosome, causes sugar build up and impairs cell function. Complete absence of functionality in this enzyme leads to death during early childhood due to deterioration of the central nervous system. Enzymes with low residual activity lead to a milder type of the disease, with symptoms like reduced hearing, mental disabilities, susceptibility to bacterial infections, and skeletal deformities. The course of the disease is progressive.

Alpha-mannosidosis is classified into types I through III based on severity and age of onset. In contrast to the usual classifications scheme of these disorders, type III is the most severe.

Tricho-hepato-enteric syndrome is one particular form of intractable diarrhea of infancy, presenting typically in the first month of life. These babies were usually born small for their age and continue to experience failure to thrive, usually with a final short stature. Typical facial features include prominent forehead and cheeks, a broad nasal root and widely spaced eyes (hypertelorism). Their hairs are woolly, easily removed and poorly pigmented. Liver disease is mainly present as cirrhosis or fibrosis, and staining might reveal high iron content of the liver cells (consistent with hemochromatosis). Most evaluated patients had some degree of decrease in intelligence.

Sack–Barabas syndrome is an older name for the medical condition Ehlers-Danlos syndrome, vascular type. It affects the body's blood vessels and organs, making them prone to rupture.

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.

Mucolipidosis type I (ML I) or sialidosis is an inherited lysosomal storage disease that results from a deficiency of the enzyme alpha-N -acetyl neuraminidase (sialidase). The lack of this enzyme results in an abnormal accumulation of complex carbohydrates known as mucopolysaccharides, and of fatty substances known as mucolipids. Both of these substances accumulate in bodily tissues.

Occipital horn syndrome (OHS), formerly considered a variant of Ehlers-Danlos syndrome, is an X-linked recessive connective tissue disorder. It is caused by a deficiency in the transport of the essential mineral copper, associated with mutations in the ATP7A gene. Only about 2/3 of children with OHS are thought to have genetically inherited the disorder; the other 1/3 do not have the disease in their family history. Since the disorder is X-linked recessive the disease affects more males. This is because they do not have a second X chromosome, unlike females, so essentially are lacking the 'backup' copy with proper function. Females are much more likely to be carriers only. For a female to be affected they must carry two defective X chromosomes, not just one. The disorder is considered a milder variant of Menkes disease.

Symptoms may differ greatly, as apparently modifiers control to some degree the amount of FVII that is produced. Some affected individuals have few or no symptoms while others may experience life-threatening bleeding. Typically this bleeding disorder manifests itself as a tendency to easy bruising, nose bleeding, heavy and prolonged menstruation, and excessive bleeding after dental or surgical interventions. Newborns may bleed in the head, from the umbilicus, or excessively after circumcision. Other bleeding can be encountered in the gut, in muscles or joints, or the brain. Hematuria may occur.

While in congenital disease symptoms may be present at birth or show up later, in patients with acquired FVII deficiency symptoms typically show up in later life.

About 3-4% of patients with FVII deficiency may also experience thrombotic episodes.

Tricho-hepato-enteric syndrome (THE), also known as syndromic or phenotypic diarrhea, is an extremely rare congenital bowel disorder which manifests itself as intractable diarrhea in infants with intrauterine growth retardation, hair and facial abnormalities. Many also have liver disease and abnormalities of the immune system. The associated malabsorption leads to malnutrition and failure to thrive.

It is thought to be a genetic disorder with an autosomal recessive inheritance pattern, although responsible genes have not been found and the exact cause remains unknown. Prognosis is poor; many patients die before the age of 5 (mainly from infections or cirrhosis), although most patients nowadays survive with intravenous feeding (parenteral nutrition).

Bart syndrome is a genetic disorder characterized by the association of congenital localized absence of skin, epidermolysis bullosa, lesions of the mouth mucosa, and dystrophic nails.

The majority of patients is initially screened by enzyme assay, which is the most efficient method to arrive at a definitive diagnosis. In some families where the disease-causing mutations are known and in certain genetic isolates, mutation analysis may be performed. In addition, after a diagnosis is made by biochemical means, mutation analysis may be performed for certain disorders.