Weird Conditions

Question 1

Tuberous Sclerosis

Answer 1

Tuberous sclerosis (TS) is a genetic condition of autosomal dominant inheritance. Like neurofibromatosis, the majority of features seen in TS are neurocutaneous.

Cutaneous features
- depigmented ‘ash-leaf’ spots which fluoresce under UV light
- roughened patches of skin over lumbar spine (Shagreen patches)
- adenoma sebaceum (angiofibromas): butterfly distribution over nose
fibromata beneath nails (subungual fibromata)
- café-au-lait spots* may be seen

Neurological features

• developmental delay
• epilepsy (infantile spasms or partial)
• intellectual impairment

Also

• retinal hamartomas: dense white areas on retina (phakomata)
• rhabdomyomas of the heart
• gliomatous changes can occur in the brain lesions
• polycystic kidneys, renal angiomyolipomata
• lymphangioleiomyomatosis: multiple lung cysts

Angiomyolipomas are the most common benign tumour of the kidney. Although regarded as benign, angiomyolipomas may grow such that kidney function is impaired or the blood vessels may dilate and burst, leading to bleeding.

Tuberous sclerosis results from mutations of the TSC1 or TSC2 gene
- Encode for proteins that have a tumour suppressing effect and disruption of these gene products allows for abnormal cell proliferation in different tissues
- Kidney Manifestations: renal angiomyolipoma, renal cyst
-Renal angiomyolipoma occur in 75% of patients
RCC is less common occurring in 1-2% of adults with TSC
Everolimus (mTOR inhibitor) can be used for the management of TSC-associated brain tumours and AMLS
Surgery or embolization may be required for large AMLS or haemorrhage AMLS

Question 2

Von Hippel Lindau

Answer 2

Von Hippel-Lindau (VHL) disease is an inherited disorder characterized by the abnormal growth of both benign and cancerous tumors and cysts in many parts of the body. Tumors usually first appear in young adulthood. The types of tumors associated with VHL disease include hemangioblastomas (slow-growing tumors of the central nervous system); kidney cysts and clear cell renal cell carcinoma; pancreatic neuroendocrine tumors; pheochromocytomas (noncancerous tumors of the adrenal glands); and endolymphatic sac tumors. VHL disease is caused by a mutation in the VHL gene and is inherited in an autosomal dominant manner. Early detection and treatment of VHL disease is important, and usually involves surgical removal of tumors.[1][2]

Question 3

Neurofibromatosis

Answer 3

Neurocutaneous disorder 
Autosomal dominant 
Cafe au lait spots 
Pheochromocytoma 
NF2: acoustic neuromas or other CNS tumours 
Iris hmartomas (Lisch Noduls)

Question 4

What are the following urinary results associated with

• Urinary hydroxyproline
• Urinary porphobilinogen
• Urinary coproporphyrin
• Urinary uroporphyrin
• Urinary delta-aminolevulinic acid

Answer 4

Urinary hydroxyproline is an adequate bone marker and in situations where there are very high rates of bone turnover, such as Paget’s disease of bone which is the diagnosis here, its level is increased.

Urinary porphobilinogen is incorrect as this is increased in acute intermittent porphyria (AIP), a rare metabolic disorder that is characterised by severe abdominal pain, muscle weakness, irritability, vomiting and constipation

Urinary coproporphyrin is incorrect as its excretion is increased in patients with Dubin-Johnson syndrome to a greater degree than in patients with other hepatobiliary disorders. Given the absence of jaundice in this patient, this diagnosis is unlikely

Urinary uroporphyrin levels are high in porphyria cutanea tarda, which occurs due to uroporphyrin decarboxylase deficiency. Porphyria cutanea tarda is a rare disorder characterised by painful, blistering skin lesions that develop on sun-exposed skin, which is not described in this case.

Urinary delta-aminolevulinic acid (ALA) excretion will also be raised in urine samples from individuals with AIP (acute intermittent porphyria), but the measurement is less widely available and is not essential.