In terms of the signs/symptoms of medullary cystic kidney disease, the disease is not easy to diagnose and is uncommon. In this condition, loss of kidney function occurs slowly over time, however the following signs/symptoms could be observed in an affected individual:

Some individuals with this disease develop gout, which is a condition in which patients develop severe pain and swelling in the big toe or another joint such as the knee. If untreated, it becomes chronic and affects the joints most of the time, instead of intermittently.

Medullary cystic kidney disease (MCKD) is an autosomal dominant kidney disorder characterized by tubulointerstitial sclerosis leading to end-stage renal disease. Because the presence of cysts is neither an early nor a typical diagnostic feature of the disease, and because at least 4 different gene mutations may give rise to the condition, the name autosomal dominant tubulointerstitial kidney disease (ADTKD) has been proposed, to be appended with the underlying genetic variant for a particular individual. Importantly, if cysts are found in the medullary collecting ducts they can result in a shrunken kidney, unlike that of polycystic kidney disease. There are two known forms of medullary cystic kidney disease, mucin-1 kidney disease 1 (MKD1) and mucin-2 kidney disease/uromodulin kidney disease (MKD2). A third form of the disease occurs due to mutations in the gene encoding renin (ADTKD-REN), and has formerly been known as familial juvenile hyperuricemic nephropathy type 2.

While most cases of horseshoe kidneys are asymptomatic and discovered upon autopsy, the condition may increase the risk for:

- Kidney obstruction – abnormal placement of ureter may lead to obstruction and dilation of the kidney.

- Kidney infections – associated with vesicoureteral reflux.

- Kidney stones – deviant orientation of kidneys combined with slow urine flow and kidney obstruction may lead to kidney stones.

- Kidney cancer – increased risk of renal cancer, especially Wilms' tumor, transitional cell carcinoma, and an occasional case report of carcinoid tumor. Despite increased risk, the overall risk is still relatively low.

The prevalence of horseshoe kidneys in females with Turner Syndrome is about 15%.

It can be associated with trisomy 18.

It can be associated with venous anomalies like left sided IVC 9.

In patients with this condition, the central portion of the kidney may be found just inferior to the inferior mesenteric artery because the normal embryologic ascent of the kidneys is arrested by its presence in people with central fusion of the kidneys. Horseshoe kidney is often asymptomatic, though persons affected by this condition may experience nausea, abdominal discomfort, kidney stones and urinary tract infections at greater frequency than those without renal fusion. There is currently no treatment for renal fusion other than symptomatic treatment.

Imaging Findings -

The 2 kidneys on opposite sides of the body with the lower poles fused in midline. Midline or symmetrical fusion (90% of cases).

May be missed on US, therefore pay careful attention to identification of lower poles of kidneys.

Renal long axis medially orientated,

Lower poles with curved configuration, elongation and poorly defined

Isthmus crosses midline anterior to spine and great vessels.

US for diagnosis in utero

IVP followed by CT or scintigraphy for pre-operative assessment

Variant arterial supply -

Bilateral renal arteries,

Inferior mesenteric Artery,

Arteries arising from aorta or common iliac, internal iliac, external iliac or inferior mesenteric arteries.

The lower poles of these kidneys fuse in the midline anterior to the aorta and spine. The isthmus is usually located at L4/5 level between the aorta and IMA.

Nuclear medicine (DMSA) scan confirms horseshoe kidney with fusion of both renal lower poles.

The symptoms of SSADH deficiency fall into three primary categories: neurological, psychiatric, and ocular. The most constant features seen are developmental delay, hypotonia and intellectual disability. Nearly half of patients seen manifest ataxia, behavior problems, seizures, and hyporeflexia.

The age of onset ranges from newborn period to 25 years. Problems unique to neonates can include prematurity, lethargy, decreased sucking, respiratory difficulty and hypoglycemia. Gastrointestinal symptoms have been seen primarily in this

population and are usually related to increased feeding.

Ocular problems related to the disorder include strabismus, nystagmus, retinitis, disc pallor, and oculomotor apraxia.

Over half of the patients with SSADH deficiency have seizures. These include absence, tonic clonic, and convulsive status epilepticus. It is unclear whether decreased levels of GABA or elevated levels of GHB are responsible for these seizures but alterations in these neurotransmitters and their receptor binding or neurotransmitter transport is hypothesized to play a role in the pathogenesis of the seizures in this population.

Symptoms associated with SSADH may be mild, moderate or severe and often vary greatly from case to case. The symptoms of SSADH are caused by the accumulation of GHB in the brain and include the following manifestations (Defined as: common, > 70% of patients; frequent 30-70% of patients;unusual, < 30% of patients):

Common manifestations include:

- Delayed gross motor development

- Delayed mental development

- Delayed fine motor skill development

- Delayed speech and language development

- Hypotonia

Frequent manifestations include:

- Seizures

- Hyporeflexia

- Ataxia

- Behavioral problems

- Hyperkinesis

Unusual manifestations include:

- Neonatal problems

- EEG abnormalities

- Psychoses

- MRI or X-ray computed tomography abnormalities

- Oculomotor apraxia

- Microcephaly

- Macrocephaly

- Hyperreflexia

- Somnolence

- Choreoathetosis

- Myopathy

Succinic semialdehyde dehydrogenase deficiency (SSADHD), also known as 4-hydroxybutyric aciduria or gamma-hydroxybutyric aciduria, is a rare autosomal recessive disorder of the degradation pathway of the inhibitory neurotransmitter γ-aminobutyric acid, or GABA. The disorder has been identified in approximately 350 families, with a significant proportion being consanguineous families. The first case was identified in 1981 and published in a Dutch clinical chemistry journal that highlighted a person with a number of neurological conditions such as delayed intellectual, motor, speech, and language as the most common manifestations. Later cases reported in the early 1990s began to show that hypotonia, hyporeflexia, seizures, and a nonprogressive ataxia were frequent clinical features as well.

SSADH deficiency is caused by an enzyme deficiency in GABA degradation. Under normal conditions, SSADH works with the enzyme GABA transaminase to convert GABA to succinic acid. Succinic acid can then be utilized for energy production via the Krebs cycle. However, because of the deficiency, the final intermediate of the GABA degradation pathway, succinic semialdehyde, accumulates and cannot be oxidized to succinic acid and is therefore reduced to gamma-hydroxybutyric acid (GHB) by gamma-hydroxybutyric dehydrogenase. This causes elevations in GHB and is believed to be the trademark of this disorder and cause for the neurological manifestations seen.