Klinefelter syndrome (KS), the most common human sex chromosome disorder 47,XXY. It is characterized by hypogonadism (micro-orchidism, oligospermia/azoospermia) and gynecomastia in late puberty. If Klinefelter syndrome is not diagnosed prenatally, a patient with 47,XXY karyotype may demonstrate various subtle, age-related clinical signs that would prompt diagnostic testing. These include the following:
Infants: Hypospadias, small phallus, cryptorchidism.
Toddlers: Developmental delay (especially expressive language skills), hypotonia.
Older boys and adolescent males: Tall stature; delayed or incomplete pubertal development with eunuchoid body habitus; gynecomastia; small, firm testes; sparse body hair.

From childhood with progression to early puberty, the pituitary-gonadal function observed is within normal limits for 47,XXY males.
At mid puberty and later, follicle-stimulating hormone (FSH) and luteinizing hormone (LH) concentrations rise to hyper-gonadotropic levels, inhibin B levels fall until they are undetectable, and testosterone levels are at low or low-normal levels after an initial increase.

Fragile X syndrome, also termed Martin-Bell syndrome or marker X syndrome, is the most common cause of inherited mental retardation, intellectual disability, and autism.
However, the patient here does not have any mental disabilities as he already works as a clerk, and that too would make Down’s Syndrome less likely.

Classic Kallmann syndrome (KS) and idiopathic hypogonadotropic hypogonadism (IHH) are rare genetic conditions that encompass the spectrum of isolated hypogonadotropic hypogonadism. Most patients have gonadotropin-releasing hormone (GnRH) deficiency, as suggested by their response to pulsatile GnRH therapy. Hypothalamic-pituitary function is otherwise normal in most patients, and hypothalamic-pituitary imaging reveals no space-occupying lesions. By definition, either anosmia or severe hyposmia is present in patients with Kallmann syndrome, in contrast to patients with idiopathic hypogonadotropic hypogonadism, whose sense of smell is normal.

A 10 year old child, with a history of URTI and haematuria, presents a picture consistent with a diagnosis of IgA nephropathy. This condition can present with proteinuria and generalized swelling. However, an important differentiating point from rapidly progressive GN is the duration. IgA nephropathy is usually <10 days (commonly 4-5 day history of infection).

All the above side-effects, with the exception of alopecia, may be seen in patients taking lithium.

Common lithium side effects may include:
– dizziness, drowsiness;
– tremors in your hands;
– trouble walking;
– dry mouth, increased thirst or urination;
– nausea, vomiting, loss of appetite, stomach pain;
– cold feeling or discoloration in your fingers or toes;
– rash; or.
– blurred vision.

Peutz-Jegher syndrome is an autosomal dominant condition which is characterised by perioral pigmentation and hamartomas of the bowel. It was initially assumed that these did not predispose to malignancy, but due to recent studies, the opposite is now believed to be true.

Sarcoidosis is a multisystem granulomatous disorder which may involve the kidneys to a variable degree. Renal calculi have been reported to occur in about 10% of patients with chronic sarcoidosis. Hypercalcaemia due to marked hyperabsorption of dietary calcium, bone resorption and renal tubular calcium reabsorption causes hypercalciuria. Both hypercalcemia and hypercalciuria contribute to nephrolithiasis.

CMV infection is usually asymptomatic in adults. However, if the mother is infected for the first time during pregnancy then there is high chances of this infection passing on to the foetus. CMV infection can cause blindness, deafness, learning difficulties, restricted growth etc. Hepatitis B, herpes simplex, syphilis and HIV do not present with these classical signs of CMV infection in new-borns. It is estimated that 10 stillbirths occur in England and Wales every year due to CMV infection. The foetus is most at risk in early pregnancy. There is no effective prevention.

The history is suggestive of scleroderma renal crisis, where we would expect thrombotic microangiopathy process with vascular endothelium involvement manifesting as mucoid intimal thickening or onion skin effect.

The combination of good comprehension but poor speech quality in this patient is consistent with damage to the Broca’s area. The Wernicke’s area is responsible for the understanding of speech, and so is not consistent with this patient.

Osteopenia is an early sign of bone weakening that is less severe than osteoporosis.
The numerical result of the bone density test is quantified as a T score. The lower the T score, the lower the bone density. T scores greater than -1.0 are considered normal and indicate healthy bone. T scores between -1.0 and -2.5 indicate osteopenia. T scores lower than -2.5 indicate osteoporosis.
DEXA also provides the patient’s Z-score, which reflects a value compared with that of person matched for age and sex.
Z-score values of -2.0 SD or lower are defined as below the expected range for age and those above -2.0 SD as within the expected range for age.

The best treatment for the patient in question would be methylene blue.
The most probable diagnosis in this patient is methemoglobinemia due to the ingestion of amyl nitrate.

Amyl nitrate promotes the formation of methaemoglobin, which avidly conserves oxygen and leads to decreased tissue oxygen saturations.

Treatment of choice includes methylene blue and vitamin C.

Adverse effects:
Benign side effects include green or blue discoloration of urine and patients should be forewarned.
Significant side effects are based on methylene blue, itself, being an oxidizing agent and an inhibitor of monoamine oxidase A (MAO-A).
As an oxidizing agent, methylene blue can actually precipitate methemoglobinemia or haemolysis in high doses or when ineffectively reduced.
Methylene blue administration in a patient taking a serotonergic agents may predispose to serotonin syndrome.

Note: Although methylene blue administration is controversial in the setting of G6PD-deficiency due to reduced levels of NADPH, it is not contraindicated and should be administered cautiously and judiciously.