Glycogen storage disease VII is an autosomal recessive metabolic disorder characterized clinically by exercise intolerance, muscle cramping, exertional myopathy, and compensated hemolysis. Myoglobinuria may also occur. The deficiency of the muscle isoform of PFK results in a total and partial loss of muscle and red cell PFK activity, respectively. Raben and Sherman (1995) noted that not all patients with GSD VII seek medical care because in some cases it is a relatively mild disorder.

Glycogen storage disease type I (GSDI) is characterized by accumulation of glycogen and fat in the liver and kidneys resulting in hepatomegaly and nephromegaly. Severely affected infants present in the neonatal period with severe hypoglycemia due to fasting intolerance. More commonly, untreated infants present at age three to four months with hepatomegaly, severe hypoglycemia with or without seizures, lactic acidosis, hyperuricemia, and hypertriglyceridemia. Affected children typically have doll-like faces with full cheeks, relatively thin extremities, short stature, and a protuberant abdomen. Xanthoma and diarrhea may be present. Impaired platelet function and development of reduced or dysfunctional von Willebrand factor can lead to a bleeding tendency with frequent epistaxis and menorrhagia in females. Individuals with untreated GSDIb are more likely to develop impaired neutrophil and monocyte function as well as chronic neutropenia resulting in recurrent bacterial infections, gingivitis, periodontitis, and genital and intestinal ulcers. Long-term complications of untreated GSDI include short stature, osteoporosis, delayed puberty, renal disease (including proximal and distal renal tubular acidosis, renal stones, and renal failure), gout, systemic hypertension, pulmonary hypertension, hepatic adenomas with potential for malignancy, pancreatitis, and polycystic ovaries. Seizures and cognitive impairment may occur in individuals with prolonged periods of hypoglycemia. Normal growth and puberty are expected in treated children. Most affected individuals live into adulthood.

Glycogenosis due to glucose-6-phosphatase deficiency (G6P) type b, or glycogen storage disease (GSD) type 1b, is a type of glycogenosis due to G6P deficiency (see this term).

The 17q12 recurrent deletion syndrome is characterized by variable combinations of the three following findings: structural or functional abnormalities of the kidney and urinary tract, maturity-onset diabetes of the young type 5 (MODY5), and neurodevelopmental or neuropsychiatric disorders (e.g., developmental delay, intellectual disability, autism spectrum disorder, schizophrenia, anxiety, and bipolar disorder). Using a method of data analysis that avoids ascertainment bias, the authors determined that multicystic kidneys and other structural and functional kidney anomalies occur in 85% to 90% of affected individuals, MODY5 in approximately 40%, and some degree of developmental delay or learning disability in approximately 50%. MODY5 is most often diagnosed before age 25 years (range: age 10-50 years).

Autosomal dominant tubulointerstitial kidney disease – MUC1 (ADTKD-MUC1) is characterized by slowly progressive tubulointerstitial disease that leads to end-stage renal disease (ESRD) and the need for dialysis or kidney transplantation. The rate of loss of kidney function for individuals is variable within and between families, with a median age of onset of end-stage renal disease (ESRD) of 46 years (range: ages 20-70 years). There are no other systemic manifestations.

Any coronary artery disease in which the cause of the disease is a mutation in the LRP6 gene.

Phosphoribosylpyrophosphate synthetase (PRS) superactivity comprises two phenotypes, both characterized by hyperuricemia and hyperuricosuria. The mild phenotype (~75% of affected males) with onset in the second or third decade of life is typically limited to these biochemical findings, whereas the severe phenotype (~25% of affected males) with onset in the first decade of life has in addition to these biochemical findings variable combinations of developmental delay (DD) / intellectual disability (ID), sensorineural hearing loss, hypotonia, and ataxia. In the mild phenotype, uric acid crystalluria or a urinary stone is commonly the first clinical finding, followed later by gouty arthritis if serum urate concentration is not controlled.

Glycogen storage disease type I (GSDI) is characterized by accumulation of glycogen and fat in the liver and kidneys resulting in hepatomegaly and nephromegaly. Severely affected infants present in the neonatal period with severe hypoglycemia due to fasting intolerance. More commonly, untreated infants present at age three to four months with hepatomegaly, severe hypoglycemia with or without seizures, lactic acidosis, hyperuricemia, and hypertriglyceridemia. Affected children typically have doll-like faces with full cheeks, relatively thin extremities, short stature, and a protuberant abdomen. Xanthoma and diarrhea may be present. Impaired platelet function and development of reduced or dysfunctional von Willebrand factor can lead to a bleeding tendency with frequent epistaxis and menorrhagia in females. Individuals with untreated GSDIb are more likely to develop impaired neutrophil and monocyte function as well as chronic neutropenia resulting in recurrent bacterial infections, gingivitis, periodontitis, and genital and intestinal ulcers. Long-term complications of untreated GSDI include short stature, osteoporosis, delayed puberty, renal disease (including proximal and distal renal tubular acidosis, renal stones, and renal failure), gout, systemic hypertension, pulmonary hypertension, hepatic adenomas with potential for malignancy, pancreatitis, and polycystic ovaries. Seizures and cognitive impairment may occur in individuals with prolonged periods of hypoglycemia. Normal growth and puberty are expected in treated children. Most affected individuals live into adulthood.

Autosomal dominant tubulointerstitial kidney disease-5 (ADTKD5) is characterized by the onset of progressive chronic renal disease in the first decades of life. Mild hyperuricemia may be present, but gout, hypertension, and proteinuria are usually absent. The disease may be associated with anemia or neutropenia. Some patients may have additional findings, including poor overall growth and impaired cognitive function. Renal biopsy shows tubulointerstitial abnormalities with atrophic tubules and fibrosis; secondary glomerular abnormalities and simple cysts may also be present (summary by Bolar et al., 2016). For a discussion of genetic heterogeneity and revised nomenclature of ADTKD, see ADTKD1 (162000).

Autosomal dominant tubulointerstitial kidney disease – UMOD (ADTKD-UMOD) is characterized by normal urinalysis and slowly progressive chronic kidney disease (CKD), usually first noted in the teen years and progressing to end-stage renal disease (ESRD) between the third and seventh decades. Hyperuricemia is often present from an early age, and gout (resulting from reduced kidney excretion of uric acid) occurs in the teenage years in about 8% of affected individuals and develops in 55% of affected individuals over time.

Autosomal dominant polycystic kidney disease (ADPKD) is generally a late-onset multisystem disorder characterized by bilateral kidney cysts, liver cysts, and an increased risk of intracranial aneurysms. Other manifestations include: cysts in the pancreas, seminal vesicles, and arachnoid membrane; dilatation of the aortic root and dissection of the thoracic aorta; mitral valve prolapse; and abdominal wall hernias. Kidney manifestations include early-onset hypertension, kidney pain, and kidney insufficiency. Approximately 50% of individuals with ADPKD have end-stage kidney disease (ESKD) by age 60 years. The prevalence of liver cysts increases with age and occasionally results in clinically significant severe polycystic liver disease (PLD), most often in females. Overall, the prevalence of intracranial aneurysms is fivefold higher than in the general population and further increased in those with a positive family history of aneurysms or subarachnoid hemorrhage. There is substantial variability in the severity of kidney disease and other extra-kidney manifestations.

Familial partial lipodystrophy type 8 (FPLD8) is an autosomal dominant disorder characterized by abnormal distribution of subcutaneous adipose tissue. Affected individuals showed selective loss of subcutaneous adipose tissue from the limbs, resulting in a muscular appearance, beginning around 13 to 15 years of age. There is also abnormal accumulation of subcutaneous adipose tissue in the dorsal neck and face, as well as in the posterior thoracic and abdominal regions. The disorder is associated with metabolic abnormalities, including diabetes mellitus and hyperlipidemia (Garg et al., 2016). For a general description and a discussion of genetic heterogeneity of familial partial lipodystrophy (FPLD), see 151660.