Detection usually begins with a routine doctor visit when the fundal height is being measured or during an ultrasound examination. When large for gestational age fetuses (LGA) are identified, there are two common causes: maternal diabetes or incorrect dates. However, if these two causes can be ruled out, an ultrasound is performed to detect for overgrowth and other abnormalities. At this point, it becomes essential for a clinical geneticist to assist in the correct selection of tests and possible diagnosis.

First signs of SGBS may be observed as early as 16 weeks of gestation. Aids to diagnosing might include the presence of macrosomia, polyhydramnios, elevated maternal serum-α-fetoprotein, cystic hygroma, hydrops fetalis, increased nuchal translucency, craniofacial abnormalities, visceromegaly, renal abnormalities, congenital diaphragmatic hernia, polydactyly, and a single umbilical artery.

If there is a known mutation in the family, prenatal testing is available. Prenatal testing is also possible by looking for evidence of the mild SGBS phenotype in the mother and the positive SGBS phenotype in male family members. Family members who are positive of SGBS may undergo mutational analysis of genes GCP3, GCP4, and CXORF5. Genomic balance in Xp22 and Xq26 may also be analyzed through array comparative genomic hybridization.

Due to the high percentage of male deaths during the neonatal period, early detection of tumors is crucial. In order to detect the presence of tumors, screening in SGBS patients should include abdominal ultrasound, urinalysis, and biochemical markers that screen for embryonic tumors.

Once the infant is born, possibility of hypoglycemia must be assessed along with cardiac, genitalia, liver, and adrenal evaluations. Such tests include chest radiographs, electrocardiogram, echocardiogram, renal sonography, and abdominal sonography to test for possible abnormalities.

Arts syndrome should be included in the differential diagnosis of infantile hypotonia and weakness aggravated by recurrent infection with a family history of X-linked inheritance. Sequence analysis of PRPS1, the only gene associated with Arts syndrome, has detected mutations in both kindreds reported to date. Arts syndrome patients were also found to have reduced levels of hypoxanthine levels in urine and uric acid levels in the serum. In vitro, PRS-1 activity was reduced in erythrocytes and fibroblasts.

There are two types of SGBS, each found on a different gene:

SGBS is also considered to be an overgrowth syndrome (OGS). OGS is characterized by a 2-3 standard deviation increase in weight, height, or head circumference above the average for sex and age. One of the most noted features of OGS is the increased risk of neoplasms in certain OGSs. SGBS in particular has been found to have a 10% tumor predisposition frequency with 94% of cases occurring in the abdominal region, most being malignant. It is common for tumors to be embryonal in type and appear before the age of 10.

There are five different types of tumors that patients with SGBS might develop, all intra-abdominal: Wilms tumor, Hepatoblastoma, Hepatocarcinoma, Gonadoblastoma, and Neuroblastoma.

The most common types of tumors developed in patients are the Wilms tumor and hepatoblastoma.

Until recently, doctors have diagnosed patients with FHS based on clinical observations and how well they fit the disease description, usually occurring in early childhood. Molecular genetic testing is also used now to test for genetic mutations. By performing a sequence analysis test of select exons, mutations can be detected in exon 34 of the SRCAP gene. This mutation has been observed in 19 patients to date.

In most cases, if the patient shows classic facial features of FHS, the molecular testing will show a mutation on the SRCAP gene.

FHS shares some common features with Rubinstein–Taybi (due to overlapping effects of mutations on SRCAP), however cranial and hand anomalies are distinctive: broad thumbs, narrow palate, and microcephaly are absent in Floating-Harbor Syndrome. One child in the UK has a diagnosis of microcephaly alongside Floating–Harbor syndrome.

According to Clinicaltrials.gov, there are no current studies on hyperglycerolemia.

Clinicaltrials.gov is a service of the U.S. National Institutes of Health. Recent research shows patients with high concentrations of blood triglycerides have an increased risk of coronary heart disease. Normally, a blood glycerol test is not ordered. The research was about a child having elevated levels of triglycerides when in fact the child had glycerol kinase deficiency. This condition is known as pseudo-hypertriglyceridemia, a falsely elevated condition of triglycerides. Another group treated patients with elevated concentrations of blood triglycerides with little or no effect on reducing the triglycerides. A few laboratories can test for high concentrations of glycerol, and some laboratories can compare a glycerol-blanked triglycerides assay with the routine non-blanked method. Both cases show how the human body may exhibit features suggestive of a medical disorder when in fact it is another medical condition causing the issue.

Glycerol and glycerol kinase activity analyses are usually not offered by routine general medical laboratories. To diagnose hyperglycerolemia, blood and urine can be tested for the amounts of glycerol present.

There are three clinical forms of GKD: infantile, juvenile, and adult. The infantile form is associated with severe developmental delay and results in a syndrome with Xp21 gene deletion with congenital adrenal hypoplasia and/or Duchenne muscular dystrophy. The infantile diagnosis is made by measuring plasma glycerol and is characterized by glycerol levels between 1.8 and 8.0 mmol/L and glyceroluria more than 360 mmol/24h. To confirm the diagnosis, genetic testing of the Xp21 gene is definitive. Children with GKD have severe hypoglycemic episodes and profound metabolic acidosis, or are completely symptom free. Individuals who are unable to form glucose from the glycerol released during triglyceride catabolism also the hypoglycemic episodes often disappear during adolescence. Patients with the juvenile and adult forms often have no symptoms and are diagnosed fortuitously when a medical professional tests for another medical condition. The juvenile form is an uncommon form characterized by Reye syndrome-like clinical manifestations including episodic vomiting, acidemia, and disorders of consciousness.

Currently, purine replacement via S-adenosylmethionine (SAM) supplementation in people with Arts syndrome appears to improve their condition. This suggests that SAM supplementation can alleviate symptoms of PRPS1 deficient patients by replacing purine nucleotides and open new avenues of therapeutic intervention. Other non-clinical treatment options include educational programs tailored to their individual needs. Sensorineural hearing loss has been treated with cochlear implantation with good results. Ataxia and visual impairment from optic atrophy are treated in a routine manner. Routine immunizations against common childhood infections and annual influenza immunization can also help prevent any secondary infections from occurring.

Regular neuropsychological, audiologic, and ophthalmologic examinations are also recommended.

Carrier testing for at-risk relatives and prenatal testing for pregnancies at increased risk are possible if the disease-causing mutation in the family is known.

The diagnosis of Perlman syndrome is based on observed phenotypic features and confirmed by histological examination of the kidneys. Prenatal diagnosis is possible for families that have a genetic disposition for Perlman syndrome although there is no conclusive laboratory test to confirm the diagnosis. Fetal overgrowth, particularly with an occipitofrontal circumference (OFC) greater than the 90th centile for gestational age, as well as an excess of amniotic fluid in the amniotic sac (polyhydramnios), may be the first signs of Perlman. Using ultrasound diagnosis, Perlman syndrome has been detected at 18 weeks. During the first trimester, the common abnormalities of the syndrome observed by ultrasound include cystic hygroma and a thickened nuchal lucency. Common findings for the second and third trimesters include macrosomia, enlarged kidneys, renal tumors (both hamartoma and Wilms), cardiac abnormalities and visceromegaly.

Prompt recognition and identification of the disorder along with accurate follow-up and clinical assistance is recommended as the prognosis for Perlman is severe and associated with a high neonatal death rate.

Familial dysautonomia is inherited in an autosomal recessive pattern, which means 2 copies of the gene in each cell are altered. If both parents are shown to be carriers by genetic testing, there is a 25% chance that the child will produce FD. Prenatal diagnosis for pregnancies at increased risk for FD by amniocentesis (for 14–17 weeks) or chorionic villus sampling (for 10–11 weeks) is possible.

Sotos syndrome is not a life-threatening disorder and patients may have a normal life expectancy. Developmental delays may improve in the school-age years; however, coordination problems may persist into adulthood, along with any learning disabilities and/or other physical or mental issues.

Screening for melanoma in FAMMM kindreds should begin at age 10 with a baseline total body skin examination including scalp, eyes, oral mucosa, genital area, and nail, as family members may develop melanoma in their early teens.

At Mayo Clinic, FAMMM patients with a confirmed mutation and family history of pancreatic cancer are offered screening with either high-resolution pancreatic protocol CT, MRI, or endoscopic ultrasound starting at age 50 or 10 years younger than the earliest family member with pancreas cancer. They are counseled on the lack of evidence-based data to support screening, and on the limitations of our current technology to detect a lesion at a stage amenable to therapy.

Standard of care for treatment of CPT II deficiency commonly involves limitations on prolonged strenuous activity and the following dietary stipulations:

- The medium-chain fatty acid triheptanoin appears to be an effective therapy for adult-onset CPT II deficiency.

- Restriction of lipid intake

- Avoidance of fasting situations

- Dietary modifications including replacement of long-chain with medium-chain triglycerides supplemented with L-carnitine

Individuals presenting with Type III galactosemia must consume a lactose- and galactose-restricted diet devoid of dairy products and mucilaginous plants. Dietary restriction is the only current treatment available for GALE deficiency. As glycoprotein and glycolipid metabolism generate endogenous galactose, however, Type III galactosemia may not be resolved solely through dietary restriction.

There are very few ways to test a patient for HGF. Currently, the most common way to diagnose a patient is by means of a physical evaluation. The physician can make a physical evaluation of the patient and send them to a dentist or better yet a specialist like a periodontist to evaluate signs of gingival overgrowth, quality of gingiva, inflammation, mechanical difficulties of the mouth, tooth conditions, and any sort of discomfort.

Aside from obvious physical symptoms seen in a physical evaluation, molecular tests can be run to check if there is a mutation in the SOS1 gene to confirm the diagnosis. If there is indeed a mutation in this gene coupled with the typical physical symptoms, then it is quite probable that a patient suffers from this disease. Also, looking at family history is also becoming more prominent in aiding to diagnose the patient. Otherwise, researchers are working to find new and better ways to test for the presence of HGF.

Perlman syndrome shares clinical overlaps with other overgrowth disorders, with similarities to Beckwith–Wiedemann syndrome and Simpson-Golabi-Behmel syndrome having been particularly emphasized in scientific study. Similarities with Beckwith-Wiedemann syndrome include polyhydramnios, macrosomia, nephromegaly and hypoglycaemia. It is the distinctive facial dysmorphology of Perlman, including deep-set eyes, depressed nasal bridge, everted upper lip, and macrocephaly which allows the two conditions to be distinguished from one another. Diagnosis of Perlman syndrome also overlaps with other disorders associated with Wilms tumor, namely, Sotos syndrome and Weaver syndrome.

Treatment is symptomatic. There is no standard course of treatment for Sotos syndrome.

The usual initial investigations include chest X ray, electrocardiogram and echocardiography. Typical findings are those of an enlarged heart with non specific conduction defects. Biochemical investigations include serum creatine kinase (typically increased 10 fold) with lesser elevations of the serum aldolase, aspartate transaminase, alanine transaminase and lactic dehydrogenase. Diagnosis is made by estimating the acid alpha glucosidase activity in either skin biopsy (fibroblasts), muscle biopsy (muscle cells) or in white blood cells. The choice of sample depends on the facilities available at the diagnostic laboratory.

In the late onset form, the findings on investigation are similar to those of the infantile form with the caveat that the creatinine kinases may be normal in some cases. The diagnosis is by estimation of the enzyme activity in a suitable sample.

On May 17, 2013 the Secretary's Discretionary Advisory Committee on Heritable Diseases in Newborns and Children (DACHDNC) approved a recommendation to the Secretary of Health and Human Services to add Pompe to the Recommended Uniform Screening Panel (RUSP). The HHS secretary must first approve the recommendation before the disease is formally added to the panel.

Diagnosis of canine phosphofructokinase deficiency is similar to the blood tests used in diagnosis of humans. Blood tests measuring the total erythrocyte PFK activity are used for definitive diagnosis in most cases. DNA testing for presence of the condition is also available.

Treatment mostly takes the form of supportive care. Owners are advised to keep their dogs out of stressful or exciting situations, avoid high temperature environments and strenuous exercise. It is also important for the owner to be alert for any signs of a hemolytic episode. Dogs carrying the mutated form of the gene should be removed from the breeding population, in order to reduce incidence of the condition.

Osteomyelitis (bone infection), which is much more common than infantile cortical hyperostosis, must be excluded, since it requires urgent treatment. Other diagnoses that can mimic this disorder and need to be excluded include physical trauma, child abuse, Vitamin A excess, hyperphosphatemia, prostaglandin E1 and E2 administration, scurvy, infections (including syphilis), Ewing sarcoma, and metastatic neuroblastoma.

Most infants with infantile cortical hyperostosis are diagnosed by physical examination. X-rays can confirm the presence of bone changes and soft tissue swelling. Biopsy of the affected areas can confirm the presence of typical histopathological changes. No specific blood tests exist, but tests such as erythrocyte sedimentation rate (ESR) and alkaline phosphatase levels are often elevated. A complete blood count may show anemia (low red blood cell count) and leukocytosis (high white blood cell count). Other tests may be done to help exclude other diagnoses. Ultrasound imaging can help diagnose prenatal cases.

Prenatal screening is not typically done for FHM, however it may be performed if requested. As penetrance is high, individuals found to carry mutations should be expected to develop signs of FHM at some point in life.

Genetic testing is performed on a small sample of blood from the tested individual. The DNA is examined with a designed probe specific to the known mutations. The accuracy of the test is above 99%. Dr. Anat Blumenfeld of the Hadasah Medical center in Jerusalem identified chromosome number 9 as the responsible chromosome.

Treatments for Glycerol Kinase Deficiency are targeted to treat the symptoms because there are no permanent treatments for this disease. The main way to treat these symptoms is by using corticosteroids, glucose infusion, or mineralocorticoids. Corticosteroids are steroid hormones that are naturally produced in the adrenal glands. These hormones regulate stress responses, carbohydrate metabolism, blood electrolyte levels, as well as other uses. The mineralocorticoids, such as aldosterone control many electrolyte levels and allow the kidneys to retain sodium. Glucose infusion is coupled with insulin infusion to monitor blood glucose levels and keep them stable.

Due to the multitude of varying symptoms of this disease, there is no specific treatment that will cure this disease altogether. The symptoms can be treated with many different treatments and combinations of medicines to try to find the correct combination to offset the specific symptoms. Everyone with Glycerol Kinase Deficiency has varying degrees of symptoms and thereby requires different medicines to be used in combination to treat the symptoms; however, this disease is not curable and the symptoms can only be managed, not treated fully.

Still's disease does not affect children under 6 months old.

Hyperimmunoglobulin D syndrome in 50% of cases is associated with mevalonate kinase deficiency which can be measured in the leukocytes.