LIG4 syndrome (also known as Ligase IV syndrome) is an extremely rare condition caused by mutations in the DNA Ligase IV (LIG4) gene. Some mutations in this gene are associated with a resistance against multiple myeloma and Severe Combined Immunodeficiency. Severity of symptoms depends on the degree of reduced enzymatic activity of Ligase IV or gene expression.

As DNA ligase IV is essential in V(D)J recombination, the mechanism by which immunoglobulins, B cell and T cell receptors are formed, patients with LIG4 syndrome may suffer from less effective or defective V(D)J recombination. Some patients have a severe immunodeficiency characterized by pancytopenia, causing chronic respiratory infections and sinusitis. Clinical features also include Seckel syndrome-like facial abnormalities and microcephaly. Patients also suffer from growth retardation and skin conditions, including photosensitivity, psoriasis and telangiectasia. Although not present in all, patients may also present with hypothyroidism and type II diabetes and possibly malignancies such as acute T-cell leukemia. The clinical phenotype of LIG4 syndrome closely resembles that of Nijmegen breakage syndrome (NBS).

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.

There is substantial variability in the severity of features of A-T among affected individuals, and at different ages. The following symptoms or problems are either common or important features of A-T:

- Ataxia (difficulty with control of movement) that is apparent early but worsens in school to pre-teen years

- Oculomotor apraxia (difficulty with coordination of head and eye movement when shifting gaze from one place to the next)

- Involuntary movements

- Telangiectasia (dilated blood vessels) over the white (sclera) of the eyes, making them appear bloodshot. These are not apparent in infancy and may first appear at age 5–8 years. Telangiectasia may also appear on sun-exposed areas of skin.

- Problems with infections, especially of the ears, sinuses and lungs

- Increased incidence of cancer (primarily, but not exclusively, lymphomas and leukemias)

- Delayed onset or incomplete pubertal development, and very early menopause

- Slowed rate of growth (weight and/or height)

- Drooling particularly in young children when they are tired or concentrating on activities

- Dysarthria (slurred, slow, or distorted speech sounds)

- Diabetes in adolescence or later

- Premature changes in hair and skin

Many children are initially misdiagnosed as having ataxic cerebral palsy. The diagnosis of A-T may not be made until the preschool years when the neurologic symptoms of impaired gait, hand coordination, speech and eye movement appear or worsen, and the telangiectasia first appear. Because A-T is so rare, doctors may not be familiar with the symptoms, or methods of making a diagnosis. The late appearance of telangiectasia may be a barrier to the diagnosis. It may take some time before doctors consider A-T as a possibility because of the early stability of symptoms and signs.

The first indications of A-T usually occur during the toddler years. Children start walking at a normal age, but may not improve much from their initial wobbly gait. Sometimes they have problems standing or sitting still and tend to sway backward or from side to side. In primary school years, walking becomes more difficult, and children will use doorways and walls for support. Children with A-T often appear better when running or walking quickly in comparison to when they are walking slowly or standing in one place. Around the beginning of their second decade, children with typical forms of A-T start using a wheelchair for long distances. During school years, children may have increasing difficulty with reading because of impaired coordination of eye movement. At the same time, other problems with fine-motor functions (writing, coloring, and using utensils to eat), and with slurring of speech (dysarthria) may arise. Most of these neurologic problems stop progressing after the age of about 12 – 15 years, though involuntary movements may start at any age and may worsen over time. These extra movements can take many forms, including small jerks of the hands and feet that look like fidgeting (chorea), slower twisting movements of the upper body (athetosis), adoption of stiff and twisted postures (dystonia), occasional uncontrolled jerks (myoclonic jerks), and various rhythmic and non-rhythmic movements with attempts at coordinated action (tremors).

It is characterized by microcephaly, a distinct facial appearance, short stature, immunodeficiency, radiation sensitivity and a strong predisposition to lymphoid malignancy. NBS is caused by a mutation in the "NBS1" gene. It is thus not surprising that many of the features are similar to ataxia telangiectasia (AT), and this syndrome is sometimes termed AT-variant 1; in AT, an abnormal ATM protein, the normal correlate of which interacts with the MRE11/RAD50/NBS1 (MRN) complex.

Duarte galactosemia (also known as Duarte variant galactosemia, DG, or biochemical variant galactosemia) is an inherited condition associated with diminished ability to metabolize galactose due to a partial deficiency of the enzyme galactose-1-phosphate uridylyltransferase. Duarte galactosemia (DG) is estimated to affect close to one in 4,000 infants born in the United States. DG Is considered by most healthcare professionals to be clinically mild. It differs from classic galactosemia in that patients with Duarte galactosemia have partial GALT deficiency whereas patients with classic galactosemia have complete, or almost complete, GALT deficiency.

DG, and the possible outcomes associated with this condition, are currently not well understood. Due to regional variations in newborn screening (NBS) protocols, some infants with DG are identified by NBS but others are not. In addition, of the infants who are diagnosed, most are clinically healthy as babies and toddlers, resulting in early discharge from follow up. Many healthcare professionals believe that DG does not negatively impact development. However, some reports have indicated that children with DG may be at increased risk for some developmental problems.

Galactosemia (British galactosaemia) is a rare genetic metabolic disorder that affects an individual's ability to metabolize the sugar galactose properly. Galactosemia follows an autosomal recessive mode of inheritance that confers a deficiency in an enzyme responsible for adequate galactose degradation.

Friedrich Goppert (1870–1927), a German physician, first described the disease in 1917, with its cause as a defect in galactose metabolism being identified by a group led by Herman Kalckar in 1956.

Its incidence is about 1 per 60,000 births for people of European ancestry. In other populations the incidence rate differs. Galactosaemia is about one hundred times more common (1:480 births) within the Irish Traveller population.

Infants with DG show an impaired ability to metabolize galactose, a sugar found at high levels in breast milk, milk formula, and most dairy products. Galactose is found at low levels in many fruits, vegetables, and other foods. Galactose is also produced at low levels by the human body.

Infants with DG, who consume breast milk or formula containing the milk sugar, lactose, are usually, but not always, asymptomatic. Infants who do show symptoms, such as jaundice, typically recover quickly when switched to a low-lactose diet, such as soy formula.

Infants are routinely screened for galactosemia in the United States, and the diagnosis is made while the person is still an infant. Infants affected by galactosemia typically present with symptoms of lethargy, vomiting, diarrhea, failure to thrive, and jaundice. None of these symptoms are specific to galactosemia, often leading to diagnostic delays. Luckily, most infants are diagnosed on newborn screening. If the family of the baby has a history of galactosemia, doctors can test prior to birth by taking a sample of fluid from around the fetus (amniocentesis) or from the placenta (chorionic villus sampling or CVS).

A galactosemia test is a blood test (from the heel of the infant) or urine test that checks for three enzymes that are needed to change galactose sugar that is found in milk and milk products into glucose, a sugar that the human body uses for energy. A person with galactosemia doesn't have one of these enzymes. This causes high levels of galactose in the blood or urine.

Galactosemia is normally first detected through newborn screening, or NBS. Affected children can have serious, irreversible effects or even die within days from birth. It is important that newborns be screened for metabolic disorders without delay. Galactosemia can even be detected through NBS before any ingestion of galactose-containing formula or breast milk.

Detection of the disorder through newborn screening (NBS) does not depend on protein or lactose ingestion, and, therefore, it should be identified on the first specimen unless the infant has been transfused. A specimen should be taken prior to transfusion. The enzyme is prone to damage if analysis of the sample is delayed or exposed to high temperatures. The routine NBS is accurate for detection of galactosemia. Two screening tests are used to screen infants affected with galactosemia—the Beutler's test and the Hill test. The Beutler's test screens for galactosemia by detecting the level of enzyme of the infant. Therefore, the ingestion of formula or breast milk does not affect the outcome of this part of the NBS, and the NBS is accurate for detecting galactosemia prior to any ingestion of galactose.

Duarte galactosemia is a milder form of classical galactosemia and usually has no long term side effects.

Functional gastrointestinal disorders are very common. Globally, irritable bowel syndrome and functional dyspepsia alone may affect 16–26% of the population.

Terms such as "functional colonic disease" (or "functional bowel disorder") refer in medicine to a group of bowel disorders which are characterised by chronic abdominal complaints without a structural or biochemical cause that could explain symptoms. Other "functional" disorders relate to other aspects of the process of digestion.

The consensus review process of meetings and publications organised by the Rome Foundation, known as the Rome process, has helped to define the functional gastrointestinal disorders. Successively, the Rome I, Rome II, Rome III and Rome IV proposed consensual classification system and terminology, as recommended by the Rome Coordinating Committee. These now include classifications appropriate for adults, children and neonates / toddlers.

The current Rome IV classification, published in 2016, is as follows:

A. Esophageal Disorders

- A1. Functional chest pain

- A2. Functional heartburn

- A3. Reflux hypersensitivity

- A4. Globus

- A5. Functional dysphagia

B. Gastroduodenal Disorders

- B1. Functional dyspepsia

- B1a. Postprandial distress syndrome (PDS)

- B1b. Epigastric pain syndrome (EPS)

- B2. Belching disorders

- B2a. Excessive supragastric belching

- B2b. Excessive gastric belching

- B3. Nausea and vomiting disorders

- B3a. Chronic nausea vomiting syndrome (CNVS}

- B3b. Cyclic vomiting syndrome (CVS)

- B3c. Cannabinoid hyperemesis syndrome (CHS)

- B4. Rumination syndrome

C. Bowel Disorders

- C1. Irritable bowel syndrome (IBS)

- IBS with predominant constipation (IBS-C)

- IBS with predominant diarrhea (IBS-D)

- IBS with mixed bowel habits (IBS-M)

- IBS unclassified (IBS-U)

- C2. Functional constipation

- C3. Functional diarrhea

- C4. Functional abdominal bloating/distension

- C5. Unspecified functional bowel disorder

- C6. Opioid-induced constipation

D. Centrally Mediated Disorders of Gastrointestinal Pain

- D1. Centrally mediated abdominal pain syndrome (CAPS)

- D2. Narcotic bowel syndrome (NBS)/ Opioid-induced GI hyperalgesia

E. Gallbladder and Sphincter of Oddi disorders

- E1. Biliary pain

- E1a. Functional gallbladder disorder

- E1b. Functional biliary sphincter of Oddi disorder

- E2. Functional pancreatic sphincter of Oddi disorder

F. Anorectal Disorders

- F1. Fecal incontinence

- F2. Functional anorectal pain

- F2a. Levator ani syndrome

- F2b. Unspecified functional anorectal pain

- F2c. Proctalgia fugax

- F3. Functional defecation disorders

- F3a. Inadequate defecatory propulsion

- F3b. Dyssynergic defecation

G. Childhood Functional GI Disorders: Neonate/Toddler

- G1. Infant regurgitation

- G2. Rumination syndrome

- G3. Cyclic vomiting syndrome (CVS)

- G4. Infant colic

- G5. Functional diarrhea

- G6. Infant dyschezia

- G7. Functional constipation

H. Childhood Functional GI Disorders: Child/Adolescent

- H1. Functional nausea and vomiting disorders

- H1a. Cyclic vomiting syndrome (CVS)

- H1b. Functional nausea and functional vomiting

- H1b1. Functional nausea

- H1b2. Functional vomiting

- H1c. Rumination syndrome

- H1d. Aerophagia

- H2. Functional abdominal pain disorders

- H2a. Functional dyspepsia

- H2a1. Postprandial distress syndrome

- H2a2. Epigastric pain syndrome

- H2b. Irritable bowel syndrome (IBS)

- H2c. Abdominal migraine

- H2d. Functional abdominal pain ‒ NOS

- H3. Functional defecation disorders

- H3a. Functional constipation

- H3b. Nonretentive fecal incontinence